The Micro- and NanoBiomedical Engineering group aims at designing and developing microtools that interface biological samples at the cellular and molecular levels, for both fundamental studies and relevant healthcare applications. Such microtools range from medical microrobots to smart sensor-actuator systems. Our research topics include basic nanobiotechnology studies, organ-on-a-chip, engineered cell-based therapies to smart microrobotics and biosensing platforms.
B. Rivkin, C. Becker, B. Singh, A. Aziz, F. Akbar, A. Egunov, D.D. Karnaushenko, R. Naumann, R. Schäfer, M. Medina-Sánchez, D. Karnaushenko, and O.G. Schmidt
Existing electronically integrated catheters rely on the manual assembly of separate components to integrate sensing and actuation capabilities. This strongly impedes their miniaturization and further integration. Here, we report an electronically integrated self-assembled microcatheter. Electronic components for sensing and actuation are embedded into the catheter wall through the self-assembly of photolithographically processed polymer thin films. With a diameter of only about 0.1 mm, the catheter integrates actuated digits for manipulation and a magnetic sensor for navigation and is capable of targeted delivery of liquids. Fundamental functionalities are demonstrated and evaluated with artificial model environments and ex vivo tissue. Using the integrated magnetic sensor, we develop a strategy for the magnetic tracking of medical tools that facilitates basic navigation with a high resolution below 0.1 mm. These highly flexible and microsized integrated catheters might expand the boundary of minimally invasive surgery and lead to new biomedical applications.
F. Akbar, B. Rivkin, A. Aziz, C. Becker, D.D. Karnaushenko, M. Medina-Sánchez, D. Karnaushenko, and O.G. Schmidt
Oscillations at several hertz are a key feature of dynamic behavior of various biological entities, such as the pulsating heart, firing neurons, or the sperm-beating flagellum. Inspired by nature’s fundamental self-oscillations, we use electroactive polymer microactuators and three-dimensional microswitches to create a synthetic electromechanical parametric relaxation oscillator (EMPRO) that relies on the shape change of micropatterned polypyrrole and generates a rhythmic motion at biologically relevant stroke frequencies of up to ~95 Hz. We incorporate an Ag-Mg electrochemical battery into the EMPRO for autonomous operation in a nontoxic environment. Such a self-sufficient self-oscillating microsystem offers new opportunities for artificial life at low Reynolds numbers by, for instance, mimicking and replacing nature’s propulsion and pumping units.
A. Aziz, J. Holthof, S. Meyer, O.G. Schmidt, and M. Medina-Sánchez
The fast evolution of medical micro- and nanorobots in the endeavor to perform non-invasive medical operations in living organisms has boosted the use of diverse medical imaging techniques in the last years. Among those techniques, photoacoustic imaging (PAI), considered a functional technique, has shown to be promising for the visualization of micromotors in deep tissue with high spatiotemporal resolution as it possesses the molecular specificity of optical methods and the penetration depth of ultrasound. However, the precise maneuvering and function's control of medical micromotors, in particular in living organisms, require both anatomical and functional imaging feedback. Therefore, herein, the use of high-frequency ultrasound and PAI is reported to obtain anatomical and molecular information, respectively, of magnetically-driven micromotors in vitro and under ex vivo tissues. Furthermore, the steerability of the micromotors is demonstrated by the action of an external magnetic field into the uterus and bladder of living mice in real-time, being able to discriminate the micromotors’ signal from one of the endogenous chromophores by multispectral analysis. Finally, the successful loading and release of a model cargo by the micromotors toward non-invasive in vivo medical interventions is demonstrated.
R. Herzer, A. Gebert, U. Hempel, F. Hebenstreit, S. Oswald, C. Damm, O. G. Schmidt, and M. Medina-Sánchez
Titanium and its alloys are frequently used to replace structural components of the human body due to their high mechanical strength, low stiffness, and biocompatibility. In particular, the use of porous materials has improved implant stabilization and the promotion of bone. However, it remains unclear which material properties and geometrical cues are optimal for a proper osteoinduction and osseointegration. To that end, transparent tubular microscaffolds are fabricated, mimicking the typical pores of structural implants, with the aim of studying early bone formation and cell-material interactions at the single cell level. Here, a β-stabilized alloy Ti-45Nb (wt%) is used for the microscaffold's fabrication due to its elastic modulus close to that of natural bone. Human mesenchymal stem cell migration, adhesion, and osteogenic differentiation is thus investigated, paying particular attention to the CaP formation and cell-body crystallization, both analyzed via optical and electron microscopy. It is demonstrated that the developed platform is suited for the long-term study of living single cells in an appropriate microenvironment, obtaining in the process deeper insights on early bone formation and providing cues to improve the stability and biocompatibility of current structural implants.
P. Wrede, M. Medina-Sánchez, V. Fomin, and O.G. Schmidt
Different propulsion mechanisms have been suggested for describing the motion of a variety of chemical micromotors, which have attracted great attention in the last decades due to their high efficiency and thrust force, enabling several applications in the fields of environmental remediation and biomedicine. Bubble-recoil based motion, in particular, has been modeled by three different phenomena: capillary forces, bubble growth, and bubble expulsion. However, these models have been suggested independently based on a single influencing factor (i.e., viscosity), limiting the understanding of the overall micromotor performance. Therefore, the combined effect of medium viscosity, surface tension, and fuel concentration is analyzed on the micromotor swimming ability, and the dominant propulsion mechanisms that describe its motion more accurately are identified. Using statistically relevant experimental data, a holistic theoretical model is proposed for bubble-propelled tubular catalytic micromotors that includes all three above-mentioned phenomena and provides deeper insights into their propulsion physics toward optimized geometries and experimental conditions.
B. Rivkin, C. Becker, F. Akbar, D.D. Karnaushenko, R. Naumann, A. Mirhajivarzaneh, M. Medina-Sánchez, D. Karnaushenko, and O.G. Schmidt
The next generation of biomedical tools requires reshapeable electronics to closely interface with biological tissues. This will offer unique mechanical properties and the ability to conform to irregular geometries while being robust and lightweight. Such devices can be achieved with soft materials and thin-film structures that are able to reshape on demand. However, reshaping at the submillimeter scale remains a challenging task. Herein, shape-controlled microscale devices are demonstrated that integrate electronic sensors and electroactive polymer actuators. The fast and biocompatible actuators are capable of actively reshaping the device into flat or curved geometries. The curvature and position of the devices are monitored with strain or magnetic sensors. The sensor signals are used in a closed feedback loop to control the actuators. The devices are wafer-scale microfabricated resulting in multiple functional units capable of grasping, holding, and releasing biological tissues, as demonstrated with a neuronal bundle.
F. Striggow, L. Nadporozhskaia, B. M. Friedrich, O.G. Schmidt, and M. Medina-Sánchez
Sperm-driven micromotors, consisting of a single sperm cell captured in a microcap, utilize the strong propulsion generated by the flagellar beat of motile spermatozoa for locomotion. It enables the movement of such micromotors in biological media, while being steered remotely by means of an external magnetic field. The substantial decrease in swimming speed, caused by the additional hydrodynamic load of the microcap, limits the applicability of sperm-based micromotors. Therefore, to improve the performance of such micromotors, we first investigate the effects of additional cargo on the flagellar beat of spermatozoa. We designed two different kinds of microcaps, which each result in different load responses of the flagellar beat. As an additional design feature, we constrain rotational degrees of freedom of the cell’s motion by modifying the inner cavity of the cap. Particularly, cell rolling is substantially reduced by tightly locking the sperm head inside the microcap. Likewise, cell yawing is decreased by aligning the micromotors under an external static magnetic field. The observed differences in swimming speed of different micromotors are not so much a direct consequence of hydrodynamic effects, but rather stem from changes in flagellar bending waves, hence are an indirect effect. Our work serves as proof-of-principle that the optimal design of microcaps is key for the development of efficient sperm-driven micromotors.
A Egunov, Z Dou, DD Karnaushenko, F Hebenstreit, N Kretschmann, K. Akgün, T. Ziemssen, D. Karnaushenko*, M. Medina-Sánchez*, and O.G. Schmidt
Analytical platforms based on impedance spectroscopy are promising for non-invasive and label-free analysis of single cells as well as of their extracellular matrix, being essential to understand cell function in the presence of certain diseases. Here, an innovative rolled-up impedimetric microfulidic sensor, called sensor-in-a-tube, is introduced for the simultaneous analysis of single human monocytes CD14+ and their extracellular medium upon liposaccharides (LPS)-mediated activation. In particular, rolled-up platinum microelectrodes are integrated within for the static and dynamic (in-flow) detection of cells and their surrounding medium (containing expressed cytokines) over an excitation frequency range from 102 to 5 × 106 Hz. The correspondence between cell activation stages and the electrical properties of the cell surrounding medium have been detected by electrical impedance spectroscopy in dynamic mode without employing electrode surface functionalization or labeling. The designed sensor-in-a-tube platform is shown as a sensitive and reliable tool for precise single cell analysis toward immune-deficient diseases diagnosis